The impact of diabetes on cardiac remodelling after myocardial infarction: potential role of thyroid hormone signalling

Diabetes (DM) increases mortality after myocardial infarction and deteriorates post-ischaemic cardiac remodelling. This study investigated possible implications of thyroid hormone (TH) signalling in either reducing or preventing this response. TH signalling has a regulatory role in metabolism, cardiac function, growth and ischaemic stress. Acute myocardial infarction (AMI) was induced in age–match healthy control rats (AMI-C) and in streptozotocin (STZ)-induced type I diabetic (DM) animals (DM+AMI) using 35 mg/kg body weight while sham operated animals served as controls (SHAM). The results show that AMI in tissue hypothyroidism caused significant down-regulation of TH receptors, TRα1 and TRβ1, in the diabetic myocardium without changes in T3, T4 levels in plasma. This response was associated with increased expression of β-MHC and distinct changes in cardiac function and geometry. Ejection fractions (EF%) was decreased in DM-AMI as compared to DM+AMI animals. Systolic and diastolic chamber dimensions were increased without concomitant increase in wall thickness and thus, WTI (the ratio of LVIDd/2*Posterior Wall thickness), an index of wall stress, was significantly elevated. The absence of wall thickening in DM+AMI hearts was associated with changes in stretch-induced kinase hypertrophic signalling p38 MAPK. In contrast, ERK, p-ERK and p-p38 MAPK levels were not changed in DM+AMI as compared to non-infarcted hearts (DM+SHAM). TH administration after AMI prevented hypothyroidism and resulted in decreased β-MHC expression, increased wall thickening and normalized wall stress, while stretch-induced p38 MAPK activation was restored. The results show that diabetes can exacerbates post-ischaemic cardiac remodelling and tissue hypothyroidism and TH treatment can prevent this response and improve cardiac haemodynamics.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of Central Lancashire

Year dc:date.issued

2012

Author dc:creator

• Kalofutis, Christos

Language dc:language

en